Glaucoma is an ocular disease complex associated with an elevated pressure within the eye, i.e., elevated intraocular pressure (IOP). As a result of the elevated IOP, damage to the optic nerve, resulting in irreversible loss of visual function, may ensue. Untreated, this condition may eventually lead to blindness. Ocular hypertension, i.e., a condition of elevated IOP, without optic nerve damage or characteristic glaucomatous visual field loss, is now believed by the majority of ophthalmologists to represent the earliest phase in the onset of glaucoma. Glaucoma is among the leading causes of blindness in the U.S. today.
Drugs currently available for the control of the symptoms of glaucoma and to halt the progressive optic nerve damage are only marginally effective (Yorio (1985) J. Ocular Pharmacol. 1:397-422). Recently, the renin-angiotensin system (RAS) has been suggested as possibly playing a role in the maintenance of intraocular pressure, as the angiotensin-converting enzyme (ACE) inhibitors, captopril and SCH 33861, have been shown to lower IOP in ocular normotensive rabbits (Watkins et al. (1987) J. Ocular Pharmacol. 3:295-307) and in humans with elevated intraocular pressures (Constad et al. (1988) Am. J. Opthalmol. 105:674-677). More recently, a renin inhibitor identified as Abbott-64662 was found to decrease aqueous humor formation and lower the IOP in rabbits following topical application (Stein et al. (1989) The Pharmacologist 31:124).
The use of certain angiotensin-AII receptor antagonists in the treatment of elevated intraocular pressure and glaucoma has been disclosed in South African Patent Application 871653, to Schering, filed Mar. 6, 1987.
Conventional therapy for glaucoma has involved topical administration of pilocarpine and/or epinephrine, and more recently beta-blockers, such as Timolol, administered to the eye several times daily. For example, beta-blockers useful as antiglaucoma agents are disclosed in commonly-assigned U.S. patent application Ser. No. 07/285007, filed Dec. 15, 1988 (CC-0747).